Nucleotide excision repair DNA synthesis by excess DNA polymerase β: a potential source of genetic instability in cancer cells

2000 ◽  
Vol 14 (12) ◽  
pp. 1765-1774 ◽  
Author(s):  
Yvan Canitrot ◽  
Jean-Sébastien Hoffmann ◽  
Patrick Calsou ◽  
Hiroshi Hayakawa ◽  
Bernard Salles ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Cancer Cells ◽  
Nucleotide Excision Repair ◽  
Dna Polymerase ◽  
Genetic Instability ◽  
Excision Repair ◽  
Dna Polymerase Β ◽  
Potential Source ◽  
Nucleotide Excision

Nucleotide Excision Repair DNA Synthesis by DNA Polymerase .epsilon. in the Presence of PCNA, RFC, and RPA

Biochemistry ◽  
1995 ◽  
Vol 34 (15) ◽  
pp. 5011-5017 ◽  
Author(s):  
Mahmud K. K. Shivji ◽  
Vladimir N. Podust ◽  
Ulrich Huebscher ◽  
Richard D. Wood
Keyword(s):  
Dna Synthesis ◽  
Nucleotide Excision Repair ◽  
Dna Polymerase ◽  
Excision Repair ◽  
Dna Polymerase Epsilon ◽  
Nucleotide Excision ◽  
Polymerase Epsilon

scholarly journals Replication Factor C Recruits DNA Polymerase δ to Sites of Nucleotide Excision Repair but Is Not Required for PCNA Recruitment

2010 ◽  
Vol 30 (20) ◽  
pp. 4828-4839 ◽  
Author(s):  
René M. Overmeer ◽  
Audrey M. Gourdin ◽  
Ambra Giglia-Mari ◽  
Hanneke Kool ◽  
Adriaan B. Houtsmuller ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Nucleotide Excision Repair ◽  
Dna Polymerase ◽  
Excision Repair ◽  
Cell Protein ◽  
Replication Factor C ◽  
Replication Factor ◽  
Nucleotide Excision ◽  
Factor C ◽  
Dna Repair Synthesis

ABSTRACT Nucleotide excision repair (NER) operates through coordinated assembly of repair factors into pre- and postincision complexes. The postincision step of NER includes gap-filling DNA synthesis and ligation. However, the exact composition of this NER-associated DNA synthesis complex in vivo and the dynamic interactions of the factors involved are not well understood. Using immunofluorescence, chromatin immunoprecipitation, and live-cell protein dynamic studies, we show that replication factor C (RFC) is implicated in postincision NER in mammalian cells. Small interfering RNA-mediated knockdown of RFC impairs upstream removal of UV lesions and abrogates the downstream recruitment of DNA polymerase delta. Unexpectedly, RFC appears dispensable for PCNA recruitment yet is required for the subsequent recruitment of DNA polymerases to PCNA, indicating that RFC is essential to stably load the polymerase clamp to start DNA repair synthesis at 3′ termini. The kinetic studies are consistent with a model in which RFC exchanges dynamically at sites of repair. However, its persistent localization at stalled NER complexes suggests that RFC remains targeted to the repair complex even after loading of PCNA. We speculate that RFC associates with the downstream 5′ phosphate after loading; such interaction would prevent possible signaling events initiated by the RFC-like Rad17 and may assist in unloading of PCNA.

Cell growth analysis and nucleotide excision repair modulation in breast cancer cells submitted to a protocol using doxorubicin and paclitaxel

Life Sciences ◽  
2021 ◽  
Vol 268 ◽  
pp. 118990
Author(s):  
Franciele Faccio Busatto ◽  
Victoria Pereira Viero ◽  
Bruna Thaís Schaefer ◽  
Jenifer Saffi
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Nucleotide Excision Repair ◽  
Breast Cancer Cells ◽  
Growth Analysis ◽  
Excision Repair ◽  
Nucleotide Excision

scholarly journals Cdt2-mediated XPG degradation promotes gap-filling DNA synthesis in nucleotide excision repair

Cell Cycle ◽  
2015 ◽  
Vol 14 (7) ◽  
pp. 1103-1115 ◽  
Author(s):  
Chunhua Han ◽  
Gulzar Wani ◽  
Ran Zhao ◽  
Jiang Qian ◽  
Nidhi Sharma ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Gap Filling ◽  
Nucleotide Excision

scholarly journals A Role for DNA Polymerase β in Mutagenic UV Lesion Bypass

2002 ◽  
Vol 277 (51) ◽  
pp. 50046-50053 ◽  
Author(s):  
Laurence Servant ◽  
Christophe Cazaux ◽  
Anne Bieth ◽  
Shigenori Iwai ◽  
Fumio Hanaoka ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Genetic Instability ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Pyrimidine Dimer ◽  
Dna Polymerase Β ◽  
Lesion Bypass ◽  
Base Excision

We report here that DNA polymerase β (pol β), the base excision repair polymerase, is highly expressed in human melanoma tissues, known to be associated with UV radiation exposure. To investigate the potential role of pol β in UV-induced genetic instability, we analyzed the cellular and molecular effects of excess pol β. We firstly demonstrated that mammalian cells overexpressing pol β are resistant and hypermutagenic after UV irradiation and that replicative extracts from these cells are able to catalyze complete translesion replication of a thymine-thymine cyclobutane pyrimidine dimer (CPD). By usingin vitroprimer extension reactions with purified pol β, we showed that CPD as well as, to a lesser extent, the thymine-thymine pyrimidine-pyrimidone (6-4) photoproduct, were bypassed. pol β mostly incorporates the correct dATP opposite the 3′-terminus of both CPD and the (6-4) photoproduct but can also misinsert dCTP at a frequency of 32 and 26%, respectively. In the case of CPD, efficient and error-prone extension of the correct dATP was found. These data support a biological role of pol β in UV lesion bypass and suggest that deregulated pol β may enhance UV-induced genetic instability.

scholarly journals Nucleotide Excision Repair or Polymerase V-Mediated Lesion Bypass Can Act To Restore UV-Arrested Replication Forks in Escherichia coli

2005 ◽  
Vol 187 (20) ◽  
pp. 6953-6961 ◽  
Author(s):  
Charmain T. Courcelle ◽  
Jerilyn J. Belle ◽  
Justin Courcelle
Keyword(s):  
Dna Synthesis ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Translesion Synthesis ◽  
Replication Forks ◽  
Repair Capacity ◽  
Translesion Dna Synthesis ◽  
Pol V ◽  
Nucleotide Excision ◽  
Translesion Dna

ABSTRACT Nucleotide excision repair and translesion DNA synthesis are two processes that operate at arrested replication forks to reduce the frequency of recombination and promote cell survival following UV-induced DNA damage. While nucleotide excision repair is generally considered to be error free, translesion synthesis can result in mutations, making it important to identify the order and conditions that determine when each process is recruited to the arrested fork. We show here that at early times following UV irradiation, the recovery of DNA synthesis occurs through nucleotide excision repair of the lesion. In the absence of repair or when the repair capacity of the cell has been exceeded, translesion synthesis by polymerase V (Pol V) allows DNA synthesis to resume and is required to protect the arrested replication fork from degradation. Pol II and Pol IV do not contribute detectably to survival, mutagenesis, or restoration of DNA synthesis, suggesting that, in vivo, these polymerases are not functionally redundant with Pol V at UV-induced lesions. We discuss a model in which cells first use DNA repair to process replication-arresting UV lesions before resorting to mutagenic pathways such as translesion DNA synthesis to bypass these impediments to replication progression.

scholarly journals DNA interstrand crosslink repair during G1 involves nucleotide excision repair and DNA polymerase ζ

2006 ◽  
Vol 25 (6) ◽  
pp. 1285-1294 ◽  
Author(s):  
Sovan Sarkar ◽  
Adelina A Davies ◽  
Helle D Ulrich ◽  
Peter J McHugh
Keyword(s):  
Nucleotide Excision Repair ◽  
Dna Polymerase ◽  
Excision Repair ◽  
Interstrand Crosslink ◽  
Nucleotide Excision ◽  
Interstrand Crosslink Repair ◽  
Crosslink Repair
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